The objective of this study is to examine specific and non-specific activation of both T and B lymphocytes at the cellular and cell surface level. Activation events to be studied are antigen induced positive and negative signals for B cells and events associated with the activation in T lymphocytes in vivo and in vitro. This will be approached by using in vitro tissue culture techniques and coordinate examination of distribution of antigen receptors of the B cells involved in positive and negative aspects of the immune response. a) It is hoped to obtain information on the manner by which T cells mediate cell cooperation and the modes of control of the expression of precursor cells. b) The induction phase of an in vitro induced specific unresponsiveness will be examined at the cellular level as well as the mechanism of induction and removal of this specific unresponsiveness. Finally, c) the mechanism of B cell amplifier, for example pokeweed mitogen will be investigated using limiting dilution analysis where it is possible to determine the number of precursors expressed and the number of progeny found in each clone. Using information obtained on the nature of antigen induced positive and negative signals for expression of the immune response, attempts will be made to induce temporary and/or long-term unresponsiveness at both T ' B cell levels: perhaps using biological amplifying agents such as PWM.